High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study

{ 'indexed': { 'date-parts': [[2023, 12, 15]], 'date-time': '2023-12-15T11:43:30Z', 'timestamp': 1702640610060}, 'reference-count': 31, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2021, 4, 22]], 'date-time': '2021-04-22T00:00:00Z', 'timestamp': 1619049600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'funder': [ { 'DOI': '10.13039/501100003399', 'name': 'Science and Technology Commission of Shanghai Municipality', 'doi-asserted-by': 'publisher'}, {'DOI': '10.13039/501100018920', 'name': 'Ruijin Hospital', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:p><jats:bold>Background:</jats:bold> Coronavirus disease 2019 (COVID-19) pandemic is ' 'continuing to impact multiple countries worldwide and effective treatment options are still ' 'being developed. In this study, we investigate the potential of high-dose intravenous vitamin ' 'C (HDIVC) in the prevention of moderate COVID-19 disease ' 'aggravation.</jats:p><jats:p><jats:bold>Methods:</jats:bold> In this retrospective ' 'before-after case-matched clinical study, we compare the outcome and clinical courses of ' 'patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous ' 'injection of vitamin C, 100\xa0mg/kg/day, 1\xa0g/h, for 7\xa0days from admission) during a ' 'one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group ' 'treated without the HDIVC protocol during the preceding two months (January 18 to March 18, ' '2020). Patients in the two groups were matched in a 1:1 ratio according to age and ' 'gender.</jats:p><jats:p><jats:bold>Results:</jats:bold> The HDIVC and control groups each ' 'comprised 55 patients. For the primary outcomes, there was a significant difference in the ' 'number of patients that evolved from moderate to severe type between the two groups (HDIVC: ' '4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], <jats:italic>P</jats:italic> ' '= 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory ' 'response syndrome (SIRS) (<jats:italic>P</jats:italic> = 0.0004) during the first week and ' 'lower SIRS occurrence (2/21 vs 10/22, <jats:italic>P</jats:italic> = 0.0086) on Day 7 (6–7\xa0' 'days after admission). In addition, HDIVC group had lower C-reactive protein levels ' '(<jats:italic>P</jats:italic> = 0.005) and higher number of CD4<jats:sup>+</jats:sup> T cells ' 'from Day 0 (on admission) to Day 7 (<jats:italic>P</jats:italic> = 0.04).” The levels of ' 'coagulation indicators, including activated partial thromboplastin time and D-dimer were also ' 'improved in the HDIVC compared to the control group on Day ' '7.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> HDIVC may be beneficial in limiting ' 'disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its ' 'improvements on the inflammatory response, immune function and coagulation function. Further ' 'randomized controlled trials are required to augment these findings.</jats:p>', 'DOI': '10.3389/fphar.2021.638556', 'type': 'journal-article', 'created': {'date-parts': [[2021, 4, 22]], 'date-time': '2021-04-22T11:55:28Z', 'timestamp': 1619092528000}, 'update-policy': 'http://dx.doi.org/10.3389/crossmark-policy', 'source': 'Crossref', 'is-referenced-by-count': 27, 'title': 'High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 ' 'Pneumonia. 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Drug Discov.'}, { 'key': 'B3', 'doi-asserted-by': 'publisher', 'first-page': '954', 'DOI': '10.1016/j.chest.2017.07.014', 'article-title': 'Hydrocortisone and ascorbic acid synergistically prevent and repair ' 'lipopolysaccharide-induced pulmonary endothelial barrier dysfunction', 'volume': '152', 'author': 'Barabutis', 'year': '2017', 'journal-title': 'Chest'}, { 'key': 'B4', 'doi-asserted-by': 'publisher', 'first-page': '3286', 'DOI': '10.3390/nu12113286', 'article-title': 'The emerging role of vitamin C in the prevention and treatment of ' 'COVID-19', 'volume': '12', 'author': 'Carr', 'year': '2020', 'journal-title': 'Nutrients'}, { 'key': 'B5', 'doi-asserted-by': 'publisher', 'first-page': '574029', 'DOI': '10.3389/fimmu.2020.574029', 'article-title': 'The long history of vitamin C: from prevention of the common cold to ' 'potential aid in the treatment of COVID-19', 'volume': '11', 'author': 'Cerullo', 'year': '2020', 'journal-title': 'Front. Immunol.'}, { 'key': 'B6', 'doi-asserted-by': 'publisher', 'first-page': '118', 'DOI': '10.1007/s12026-014-8534-z', 'article-title': 'T cell-mediated immune response to respiratory coronaviruses', 'volume': '59', 'author': 'Channappanavar', 'year': '2014', 'journal-title': 'Immunol. Res.'}, { 'key': 'B7', 'doi-asserted-by': 'publisher', 'first-page': '100028', 'DOI': '10.1016/j.medidd.2020.100028', 'article-title': 'Can early and high intravenous dose of vitamin C prevent and treat ' 'coronavirus disease 2019 (COVID-19)?', 'volume': '5', 'author': 'Cheng', 'year': '2020', 'journal-title': 'Med. Drug Discov.'}, { 'key': 'B8', 'doi-asserted-by': 'publisher', 'first-page': '522', 'DOI': '10.1186/s13054-020-03249-y', 'article-title': 'Vitamin C levels in patients with SARS-CoV-2-associated acute ' 'respiratory distress syndrome', 'volume': '24', 'author': 'Chiscano-Camón', 'year': '2020', 'journal-title': 'Crit. 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Transl Med.'}, { 'key': 'B11', 'doi-asserted-by': 'publisher', 'first-page': '1261', 'DOI': '10.1001/jama.2019.11825', 'article-title': 'Effect of vitamin C infusion on organ failure and biomarkers of ' 'inflammation and vascular injury in patients with sepsis and severe ' 'acute respiratory failure', 'volume': '322', 'author': 'Fowler', 'year': '2019', 'journal-title': 'Jama'}, { 'key': 'B12', 'doi-asserted-by': 'publisher', 'first-page': '1708', 'DOI': '10.1056/NEJMoa2002032', 'article-title': 'Clinical characteristics of coronavirus disease 2019 in China', 'volume': '382', 'author': 'Guan', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B13', 'doi-asserted-by': 'publisher', 'first-page': '590853', 'DOI': '10.3389/fmed.2020.590853', 'article-title': 'Reanalysis of the effect of vitamin C on mortality in the CITRIS-ALI ' 'trial: important findings dismissed in the trial report', 'volume': '7', 'author': 'Hemilä', 'year': '2020', 'journal-title': 'Front. Med.'}, { 'key': 'B14', 'doi-asserted-by': 'publisher', 'first-page': '360', 'DOI': '10.1186/s13054-020-03077-0', 'article-title': 'The unique characteristics of COVID-19 coagulopathy', 'volume': '24', 'author': 'Iba', 'year': '', 'journal-title': 'Crit. Care'}, { 'key': 'B15', 'doi-asserted-by': 'publisher', 'first-page': '1358', 'DOI': '10.1097/ccm.0000000000004458', 'article-title': 'Coagulopathy of coronavirus disease 2019', 'author': 'Iba', 'year': '', 'journal-title': 'Crit. Care Med.'}, { 'key': 'B16', 'doi-asserted-by': 'publisher', 'first-page': '1629', 'DOI': '10.1056/NEJMoa1415236', 'article-title': 'Systemic inflammatory response syndrome criteria in defining severe ' 'sepsis', 'volume': '372', 'author': 'Kaukonen', 'year': '2015', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'B17', 'doi-asserted-by': 'publisher', 'first-page': 'm1036', 'DOI': '10.1136/bmj.m1036', 'article-title': 'Covid-19: WHO declares pandemic because of “alarming levels” of spread, ' 'severity, and inaction', 'volume': '368', 'author': 'Mahase', 'year': '2020', 'journal-title': 'Bmj'}, { 'key': 'B18', 'doi-asserted-by': 'publisher', 'first-page': '2054', 'DOI': '10.1089/ars.2012.4988', 'article-title': 'Vitamin C promotes maturation of T-cells', 'volume': '19', 'author': 'Manning', 'year': '2013', 'journal-title': 'Antioxid. 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Nutr.'}, { 'key': 'B28', 'doi-asserted-by': 'publisher', 'first-page': '934', 'DOI': '10.1001/jamainternmed.2020.0994', 'article-title': 'Risk factors associated with acute respiratory distress syndrome and ' 'death in patients with coronavirus disease 2019 pneumonia in wuhan, ' 'China', 'volume': '180', 'author': 'Wu', 'year': '2020', 'journal-title': 'JAMA Intern. Med.'}, { 'key': 'B29', 'doi-asserted-by': 'publisher', 'first-page': 'e51', 'DOI': '10.1016/j.jinf.2020.04.012', 'article-title': 'Suppressed T cell-mediated immunity in patients with COVID-19: a ' 'clinical retrospective study in Wuhan, China', 'volume': '81', 'author': 'Xu', 'year': '2020', 'journal-title': 'J. Infect.'}, { 'key': 'B30', 'first-page': '311', 'article-title': 'Hematological findings in SARS patients and possible mechanisms ' '(review)', 'volume': '14', 'author': 'Yang', 'year': '2004', 'journal-title': 'Int. J. Mol. 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